Evaluating stimulation eficacy for treating sleep apnea and lingual muscle tone sensing system for improved osa therapy

ABSTRACT

A system and method of assessing therapy of an implantable neurostimulator (INS), the INS including a lead having at least one pair of bi-polar electrodes, and a pulse generator in electrical communication with the bi-polar electrodes, the pulse generator including a sensor, a memory, a control circuit, and a telemetry circuit. The system and method includes an external programmer in communication with the INS via the telemetry circuit, a server in communication with the external programmer and including thereon an application configured to receive sensor data from the INS from the external programmer and assess a quality of the sleep of a patient in which the INS is implanted based on the received sensor data, and a remote computer in communication with the server and configured to present an assessment of the quality of sleep of the patient.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Application No.62/814,398 filed Mar. 6, 2019 and entitled INTRAMUSCULAR HYPOGLOSSALNERVE STIMULATION FOR OBSTRUCTIVE SLEEP APNEA THERAPY, the entirecontents of which are incorporated herein by reference.

TECHNICAL FIELD

This disclosure relates to a medical device system and method fortherapeutic electrical stimulation of the hypoglossal nerve fortreatment of obstructive sleep apnea. More particularly the disclosurerelates to methods of measuring lingual muscle tone and evaluatingefficacy of stimulation therapy.

BACKGROUND

Implantable medical devices capable of delivering electrical stimulationpulses have been proposed or are available for treating a variety ofmedical conditions, such as cardiac arrhythmias and chronic pain asexamples. Obstructive sleep apnea (OSA), which encompasses apnea andhypopnea, is a serious disorder in which breathing is irregularly andrepeatedly stopped and started during sleep, resulting in disruptedsleep and reducing blood oxygen levels. OSA is caused by complete orpartial collapse of the pharynx during sleep. In particular, muscles ina patient's mouth and throat intermittently relax thereby obstructingthe upper airway while sleeping. Airflow into the upper airway can beobstructed by the tongue or soft pallet moving to the back of the throatand covering a smaller than normal airway. Loss of air flow also causesunusual inter-thoracic pressure as a person tries to breathe with ablocked airway. Lack of adequate levels of oxygen during sleep cancontribute to abnormal heart rhythms, heart attack, heart failure, highblood pressure, stroke, memory problems and increased accidents.Additionally, loss of sleep occurs when a person is awakened during anapneic episode. Implantable medical devices capable of deliveringelectrical stimulation pulses have been proposed for treating OSA byelectrically stimulating muscles around the upper airway that may blockthe airway during sleep.

SUMMARY

One aspect of the disclosure is directed to an implantableneurostimulator (INS) including: an electrical lead having formedthereon at least a pair of bi-polar electrodes, where the electricallead is configured for placement of the pair of bi-polar electrodesproximate protrusor muscles of a patient and configured to receiveelectromyography (EMG) signals; a pulse generator electrically connectedto the electrical lead and configured to deliver electrical energy tothe pair of bi-polar electrodes, the pulse generator having therein asensor and a control circuit, where the sensor and control circuit areconfigured to receive the EMG signals and determine a tonal state of theprotrusor muscles in which the lead is placed. Other embodiments of thisaspect include corresponding computer systems, apparatus, and computerprograms recorded on one or more computer storage devices, eachconfigured to perform the actions of the methods and systems describedherein.

Implementations of this aspect of the disclosure may include one or moreof the following features. The implantable neurostimulator where thecontrol circuit is in electrical communication with a therapy deliverycircuit and causes the therapy delivery circuit to deliver electricalenergy to the bi-polar electrodes upon a determination that the EMGsignal is below a threshold value. The implantable neurostimulator wherethe control circuit is in electrical communication with a therapydelivery circuit and causes the therapy delivery circuit to deliverelectrical energy to the bi-polar electrodes upon a determination thatthe EMG signal is below a threshold value and a heart rate detected bythe sensor is below a threshold. The implantable neurostimulator wherethe control circuit is in electrical communication with a therapydelivery circuit and causes the therapy delivery circuit to deliverelectrical energy to the bi-polar electrodes upon a determination thatthe EMG signal is below a threshold value and a motion sensor determinesthat the INS is not moving. The implantable neurostimulator where thecontrol circuit is in electrical communication with a therapy deliverycircuit and causes the therapy delivery circuit to deliver electricalenergy to the bi-polar electrodes upon a determination that the EMGsignal is below a threshold value and an acoustic sensor detects soundsconsistent with snoring. The implantable neurostimulator where thecontrol circuit is in electrical communication with a therapy deliverycircuit and causes the therapy delivery circuit to deliver electricalenergy to the bi-polar electrodes upon a determination that the EMGsignal is below a threshold value and a temperature sensor detects abody temperature consistent with sleeping. The implantableneurostimulator where the control circuit is in electrical communicationwith a therapy delivery circuit and causes the therapy delivery circuitto deliver electrical energy to the bi-polar electrodes upon adetermination that the EMG signal is below a threshold value and abreathing rate sensor detects a breathing rate consistent with sleeping.

A further aspect of the disclosure is directed to a system including: animplantable neurostimulator (INS), including a lead having at least onepair of bi-polar electrodes, and a pulse generator in electricalcommunication with the bi-polar electrodes, the pulse generatorincluding a sensor, a memory, a control circuit, and a telemetrycircuit; an external programmer in communication with the INS via thetelemetry circuit; a server in communication with the externalprogrammer and including thereon an application configured to receivesensor data from the INS from the external programmer and assess aquality of the sleep of a patient in which the INS is implanted based onthe received sensor data; and a remote computer in communication withthe server and configured to present an assessment of the quality ofsleep of the patient. Other embodiments of this aspect includecorresponding computer systems, apparatus, and computer programsrecorded on one or more computer storage devices, each configured toperform the actions of the methods and systems described herein.

Implementations of this aspect of the disclosure may include one or moreof the following features. The system further including a user interfacepresented on the external programmer and configured to receive a varietyof self-reported data entered by the patient. The system where theapplication is further configured to assess the quality of the sleep ofa patient in which the INS is implanted based on the received sensordata and the self-reported data. The system where the assessment of thequality of sleep is presented in the form of a sleep score. The systemwhere the application is configured to assess the quality of the sleepof a patient in which the INS is implanted based on the received sensordata and self-reported data entered via a user interface on the externalprogrammer and to determine a set of suggested updated stimulationparameters for the INS. The system where the received sensor dataincludes one or more of a tonal state of protrusor muscles, heartrate,blood pressure, blood oxygen saturation, patient temperature, arousals,awakenings, and electromyography data. The system where the updatedstimulation parameters are available of review, acceptance,modification, or rejection on the remote computer. The system where uponacceptance or modification of the updated stimulation parameters, theupdated stimulation parameters are transmitted to the externalprogrammer. The system where the external programmer transmits theupdated stimulation parameters to the INS.

Still a further aspect of the disclosure is directed to a method ofproviding feedback for an implantable neurostimulator (INS), includingreceiving sensor data from an INS having at least one lead implanted ina protrusor muscle of a patient. The method also includes receivingself-reporting data entered via a user interface. The method alsoincludes analyzing the sensor and self-reported data to determine asleep score. The method also includes recording the sleep score. Themethod also includes presenting the sleep score for analysis. Otherembodiments of this aspect include corresponding computer systems,apparatus, and computer programs recorded on one or more computerstorage devices, each configured to perform the actions of the methodsand systems described herein.

Implementations of this aspect of the disclosure may include one or moreof the following features. The method further including providingsuggestions for updating stimulation parameters of the INS. The methodfurther including transmitting updated stimulation parameters to anexternal programmer associated with the INS and updating the INS. Themethod further including analyzing with an artificial intelligence theself-reported data and sensor to determine whether a reversion to thestimulation parameters of the INS prior to the update is necessary.Implementations of the described techniques may include hardware, amethod or process, or computer software on a computer-accessible medium,including software, firmware, hardware, or a combination of theminstalled on the system that in operation causes or cause the system toperform the actions. One or more computer programs can be configured toperform particular operations or actions by virtue of includingInstructions that, when executed by data processing apparatus, cause theapparatus to perform the actions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a conceptual diagram of an implantable neurostimulator (INS)for delivering OSA therapy;

FIG. 2 is a conceptual diagram of a pulse generator included in INS ofFIG. 1;

FIG. 3 is a diagram of the distal portion of the lead of the INS of FIG.1 deployed for delivering OSA therapy according to one aspect of thedisclosure;

FIG. 4 is a diagram of the distal portion of a two lead INS deployed fordelivering OSA therapy according to a further aspect of the disclosure;

FIG. 5 is a timing diagram illustrating a method performed by the systemof FIG. 1 for delivering selective stimulation to the protrusor musclesfor promoting upper airway patency during sleep according to oneexample; and

FIG. 6 is a timing diagram of a method for delivering OSA therapy by thesystem of FIG. 1 according to another example.

FIG. 7A depicts an electromyography plot of the tongue compared topharyngeal pressure during breathing;

FIG. 7B depicts the change in electromyography activity from an awake tosleep state for both normal subjects and those suffering from OSA;

FIG. 8 depicts electromyography of the tongue at different sleep andwakefulness states;

FIG. 9 depicts steps of signal processing required to transform rawelectromyography signals into useable data streams in accordance withthe present disclosure;

FIG. 10 depicts a simplified system for collecting, transmitting, andanalyzing data derived from or directed to and INS;

FIG. 11 depicts a flow chart for collecting, transmitting, and analyzingdata derived from or directed to and INS.

DETAILED DESCRIPTION

An implantable neurostimulator (INS) system for delivering electricalstimulation to the lingual muscles of the tongue, in particular theprotrusor muscles, for the treatment of OSA is described herein.Electrical stimulation is delivered to cause the tongue of a patient tobe in a protruded state, during sleep, to avoid or reduce upper airwayobstruction. As used herein, the term, “protruded state” with regard tothe tongue refers to a position that is moved forward and/or downwardcompared to the non-stimulated position or a relaxed position. Those ofskill in the art will recognize that to be in a protruded state does notrequire the tongue to be coming out of the mouth of the patient, indeedit is preferable that the tongue not extend out of the mouth of thepatient, but only be advanced forward to a point where obstruction ofthe airway is mitigated or eliminated. The protruded state is a stateassociated with the recruitment of protrusor muscles of the tongue (alsosometimes referred to as “protruder” muscles of the tongue) includingthe genioglossus and geniohyoid muscles. A protruded state may be theopposite of a retracted and/or elevated position associated with therecruitment of the retractor muscles, e.g., styloglossus and hyoglossusmuscles, which retract and elevate the tongue. Electrical stimulation isdelivered to cause the tongue to move to and maintain a protruded stateto prevent collapse, open or widen the upper airway of a patient topromote unrestricted or at least reduced restriction of airflow duringbreathing.

Current INS systems must be turned on and off manually by the patientwhen they go to sleep and wake up. As will be appreciated, manualswitching is not always a desirable feature in an implantable deviceassociated with sleeping. In accordance with one aspect of thedisclosure the INS only need to be turned on when there is a loss oflingual muscle tone (i.e., the protruder muscles are not beingsufficiently stimulated naturally). The loss of lingual muscle toneincreases the susceptibility of the patient to experience an OSA event.Accordingly, one aspect of the disclosure is directed to systems andmethods for assessing the muscle tone of the protruder muscles, based onthe tonal state determining that the patient is in need of therapy, andapplying the needed therapy. The result is a therapy system which willbe more “natural” and convenient for the patient and increase therapycompliance.

A further aspect of the disclosure is directed to systems and methods ofutilizing the sensed tonal state of the protrusor muscles along with avariety of self-reported and detected patient data to develop a patientfeedback sleep score for consultation, stimulation modification, andhealth care reimbursement support.

FIG. 1 is a conceptual diagram of an implantable neurostimulator (INS)system for delivering OSA therapy. The INS system 10 includes at leastone electrical lead 20 and a pulse generator 12. Pulse generator 12includes a housing 15 enclosing circuitry including a control circuit,therapy delivery circuit, optional sensor, a battery, and telemetrycircuit as described below in conjunction with FIG. 2. A connectorassembly 17 is hermetically sealed to housing 15 and includes one ormore connector bores for receiving at least one medical electrical leadused for delivering OSA therapy and, in some examples, for sensingphysiological conditions such as electromyogram (EMG) signals and thelike. As depicted in FIG. 1 the pulse generator 12 is implanted in theneck of the patient 8. The instant disclosure is not so limited, and thepulse generator 12 may be located in other locations such as in thechest area or other areas known to those of skill in the art.

Lead 20 includes a flexible, elongate lead body 22 that extends from alead proximal end 24 to a lead distal end 26. At least two electrodes 30are carried along a lead distal portion adjacent lead distal end 26 thatare configured for insertion within the protrusor muscles 42 a, 42 b and46 of the patient's tongue 40. The electrodes 30 are configured forimplantation within soft tissue such as musculature proximate to themedial branches of one or both hypoglossal nerves (HGN) that innervatethe protrusor muscles of the tongue. The electrodes may be placedapproximately 5 mm (e.g., from 2 mm to 8 mm) from a major trunk of theHGN. As such, the electrodes 30 may be referred to herein as“intramuscular electrodes,” in contrast to an electrode that is placedon or along a nerve trunk or branch, such as a cuff electrode, used todirectly stimulate the nerve trunk or branch. Lead 20 may be referred toherein as an “intramuscular lead” since the lead distal end andelectrodes 30 are configured for advancement through the soft tissue,which may include the protrusor muscle tissue, to anchor electrodes 30in proximity of the HGN branches that innervate the protrusor muscles 42a, 42 b and 46. The term “intramuscular” with regard to electrodes 30and lead 20 is not intended to be limiting, however, since theelectrodes 30 may be implanted in connective tissue or other soft tissueproximate the medial HGN and its branches. One or more electrodes 30 maybe placed in an area of protrusor muscles 42 a, 42 b and 46 that includemotor points, where each nerve axon terminates in the muscle (alsocalled the neuro-muscular junction). The motor points are not at onelocation but spread out in the protrusor muscles. Leads 20 may beimplanted such that one or more electrodes 30 may be generally in thearea of the motor points (e.g., such that the motor points are within 1to 10 mm from one or more electrodes 30).

The protrusor muscles are activated by electrical stimulation pulsesgenerated by pulse generator 12 and delivered via the intramuscularelectrodes 30 to move tongue 40 forward, to promote a reduction inobstruction or narrowing of the upper airway 6 during sleep. As usedherein, the term “activated” with regard to the electrical stimulationof the protrusor muscles refers to electrical stimulation that causesdepolarization or an action potential of the cells of the nerve (e.g.,hypoglossal nerve(s)) innervating the protrusor muscles and motor pointsand subsequent depolarization and mechanical contraction of theprotrusor muscle cells. In some cases, the muscles may be activateddirectly by the electrical stimulation pulses. The protrusor musclesthat may be activated by stimulation via intramuscular electrodes 30 mayinclude at least one or both of the right and/or left genioglossusmuscle (GG) 42, which includes the oblique compartment (GGo) 42 a andthe horizontal compartment (GGh) 42 b (referred to collectively as GG42) and/or the right and/or left geniohyoid muscle (GH) 46. The GGmuscle and GH muscle are innervated by a medial branch of the HGN (alsoreferred to as the XIIth cranial nerve), while the hyoglossus andstyloglossus muscles, which cause retraction and elevation of thetongue, are innervated by a lateral branch of the HGN.

The multiple distal electrodes 30 may be used to deliver bilateral orunilateral stimulation to the GG 42 and/or the GH 46 muscles via themedial branch of the HGN or branches thereof, also referred to herein asthe “medial HGN.” Distal electrodes 30 may be switchably coupled tooutput circuitry of pulse generator 12 to enable delivery of electricalstimulation pulses in a manner that selectively activates the right andleft protrusor muscles in a cyclical or alternating pattern to avoidmuscle fatigue while maintaining upper airway patency. Additionally oralternatively, electrical stimulation may be delivered to selectivelyactivate the GG 42 and/or GH 46 muscles or portions thereof duringunilateral stimulation of the left or right protrusor muscles.

The lead proximal end 24 includes a connector (not shown in FIG. 1) thatis coupleable to connector assembly 17 of pulse generator 12 to provideelectrical connection between circuitry enclosed by the housing 15 ofpulse generator 12, e.g., including therapy delivery circuitry andcontrol circuitry as described below in conjunction with FIG. 2. Thelead body 22 encloses electrical conductors extending from each of thedistal electrodes 30 to the proximal connector at proximal end 24 toprovide electrical connection between output circuitry of pulsegenerator 12 and the electrodes 30.

Though shown in FIG. 1 as separate from and extending from the pulsegenerator 12, the lead 20 could be integrated into a portion of thepulse generator 12, and merely be an exposed surface of the pulsegenerator 12. In such an embodiment, the pulse generator would beimplanted proximate the lingual muscles under the chin of the patient.In contrast the embodiment shown in FIG. 1 allows for more flexibilityin the placement of the pulse generator in the neck or pectoral regionof the patient.

FIG. 2 is a schematic diagram of pulse generator 12. Pulse generator 12includes a control circuit 80, memory 82, therapy delivery circuit 84, asensor 86, telemetry circuit 88 and power source 90. Power source 90 mayinclude one or more rechargeable or non-rechargeable batteries forsupplying electrical current to each of the control circuit 80, memory82, therapy delivery circuit 84, sensor 86 and telemetry circuit 88.While power source 90 is shown in communication only with controlcircuit 80 for the sake of clarity, it is to be understood that powersource 90 provides power as needed to each of the circuits andcomponents of pulse generator 12 as needed. For example, power source 90provides power to therapy delivery circuit 84 for generating electricalstimulation pulses.

Sensor 86 may include one or more separate sensors for monitoring apatient condition. These sensors may include one or more accelerometers,inertial measurement units (IMU), fiber-Bragg gratings (e.g., shapesensors), optical sensors, acoustic sensors, pulse oximeters, and otherswithout departing from the scope of the disclosure and as will bedescribed in greater detail below. In one aspect of the disclosuresensor 86 is configured as, among other things, a patient posturesensor. Patient posture data may be stored in memory 82 from thedetected posture states of patient when sensor 86 is included, and maybe presented on a display of external programmer 50, e.g., as generallydescribed in U.S. Pat. No. 9,662,045 (Skelton, et al.), incorporated byreference in its entirety.

Additionally or alternatively, the sensor 86 may detect a signal that iscorrelated to the movement of the patient's tongue into and out of aprotruded state. This signal may be used to detect adequate protrusionand/or fatigue of the stimulated muscle for use in controlling the dutycycle, pulse amplitude and/or stimulating electrode vector of theelectrical stimulation therapy delivered by therapy delivery circuit 84.

The functional blocks shown in FIG. 2 represent functionality includedin a pulse generator 12 configured to delivery an OSA therapy and mayinclude any discrete and/or integrated electronic circuit componentsthat implement analog and/or digital circuits capable of producing thefunctions attributed to a pulse generator herein. The various componentsmay include an application specific integrated circuit (ASIC), anelectronic circuit, a processor (shared, dedicated, or group) and memorythat execute one or more software or firmware programs, a combinationallogic circuit, state machine, or other suitable components orcombinations of components that provide the described functionality.Providing software, hardware, and/or firmware to accomplish thedescribed functionality in the context of any modern medical devicesystem, given the disclosure herein, is within the abilities of one ofskill in the art.

Control circuit 80 communicates, e.g., via a data bus, with memory 82,therapy delivery circuit 84, telemetry circuit 88 and sensor 86 (whenincluded) to control OSA therapy delivery and other pulse generatorfunctions. As disclosed herein, control circuit 80 may pass controlsignals to therapy delivery circuit 84 to cause therapy delivery circuit84 to deliver electrical stimulation pulses via electrodes 30 accordingto a therapy protocol that may include selective stimulation patterns ofright and left portions of the GG and GH muscles and/or proximal anddistal portions of the GG and GH muscles. Control circuit 80 may furtherbe configured to pass therapy control signals to therapy deliverycircuit 84 including stimulation pulse amplitude, stimulation pulsewidth, stimulation pulse number and frequency of a stimulation pulsetrain.

Memory 82 may store instructions for execution by a processor includedin control circuit 80, stimulation control parameters, and otherdevice-related or patient-related data. Control circuit 80 may retrievetherapy delivery control parameters and a therapy delivery protocol frommemory 82 to enable control circuit 80 to pass control signals totherapy delivery circuit 84 for controlling the OSA therapy. Memory 82may store historical data relating to therapy delivery for retrieval bya user via telemetry circuit 88. Therapy delivery data or informationstored in memory 82 may include therapy control parameters used todeliver stimulation pulses as well as delivered therapy protocol(s),hours of therapy delivery or the like. Patient related data, such asthat received from the sensor 86 signal may be stored in memory 82 forretrieval by a user.

Therapy delivery circuit 84 may include a charging circuit 92, an outputcircuit 94, and a switching circuit 96. Charging circuit 92 may includeone or more holding capacitors that are charged using a multiple of thebattery voltage of power source 90, for example. The holding capacitorsare switchably connected to output circuit 94, which may include one ormore output capacitors that are coupled to a selected bipolar electrodepair via switching circuit 96. The holding capacitor(s) are charged to aprogrammed pacing pulse voltage amplitude by charging circuit 92 anddischarged across the output capacitor for a programmed pulse width.Charging circuit 92 may include capacitor charge pumps or an amplifierfor the charge source to enable rapid recharging of holding capacitorsincluded in charging circuit 92. Therapy delivery circuit 84 responds tocontrol signals from control circuit 80 for generating and deliveringtrains of pulses to produce sustained tetanic contraction of the GGand/or GH muscles or portions thereof to move the tongue forward andavoid upper airway obstruction.

Output circuit 94 may be selectively coupled to bipolar pairs ofelectrodes 30 a-30 d via switching circuit 96. Switching circuit 96 mayinclude one or more switches activated by timing signals received fromcontrol circuit 80. Electrodes 30 a-30 d may be selectively coupled tooutput circuit 94 in a time-varying manner to deliver stimulation todifferent portions of the protrusor muscles at different time to avoidfatigue, without requiring stimulation to be withheld completely.Switching circuit 96 may include a switch array, switch matrix,multiplexer, or any other type of switching device(s) suitable toselectively couple therapy delivery circuit 84 to bipolar electrodepairs selected from electrodes 30. Bipolar electrode pairs may beselected one at a time or may be selected two or more at time to allowoverlapping stimulation of two or more different portions of theprotrusor muscles. Overlapping stimulation times of two portions of theprotrusor muscles, for example left and right or proximal and distal maymaintain a forward position of the tongue and allow a ramping up andramping down of the electrical stimulation being delivered to twodifferent portions of the protrusor muscles.

Telemetry circuit 88 is optional but may be included to enablebidirectional communication with an external programmer 50. A user, suchas the patient 8, may manually adjust therapy control parametersettings, e.g., as described in Medtronic's Patient Programmer Model37642, incorporated by reference in its entirety. The patient may makelimited programming changes such as small changes in stimulation pulseamplitude and pulse width. The patient may turn the therapy on and offor set timers to turn the therapy on or off using external programmer 50in wireless telemetric communication with telemetry circuit 88.

In other examples, a user, such as a clinician, may interact with a userinterface of an external programmer 50 to program pulse generator 12according to a desired OSA therapy protocol. For example, a PhysicianProgrammer Model 8840 available from Medtronic, Inc., Minneapolis,Minn., may be used by the physician to program pulse generator 12 fordelivering electrical stimulation.

Programming of pulse generator 12 may refer generally to the generationand transfer of commands, programs, or other information to control theoperation of pulse generator 12. For example, external programmer 50 maytransmit programs, parameter adjustments, program selections, groupselections, or other information to control the operation of pulsegenerator 12, e.g., by wireless telemetry. As one example, externalprogrammer 50 may transmit parameter adjustments to support therapychanges. As another example, a user may select programs or programgroups. A program may be characterized by an electrode combination,electrode polarities, voltage or current amplitude, pulse width, pulserate, therapy duration, and/or pattern of electrode selection fordelivering patterns of alternating portions of the protrusor musclesthat are being stimulated. A group may be characterized by multipleprograms that are delivered simultaneously or on an interleaved orrotating basis. These programs may adjust output parameters or turn thetherapy on or off at different time intervals.

External programmer 50 may present patient related and/or device relateddata retrieved from memory 82 via telemetry circuit 88. Additionally oralternatively, external programmer 50 may present sleep sound or motiondata stored in memory 82 as determined from signals from sensor 86.Further, the time periods in which the patient is lying down can beacquired based on patient posture detection using sensor 86 and ahistory of such data can be stored into memory 82 and retrieved anddisplayed by external programmer 50.

FIG. 3 depicts a single intramuscular lead 20 inserted into the tongue40 of a patient. Lead 20 may include two or more electrodes, and in theexample shown lead 20 includes four electrodes 30 a, 30 b, 30 c, and 30d (collectively referred to as “electrodes 30”) spaced apartlongitudinally along lead body 22. Lead body 22 is a flexible lead bodywhich may define one or more lumens within which insulated electricalconductors extend to a respective electrode 30 a-30 d. The distal mostelectrode 30 a may be adjacent or proximate to lead distal end 26. Eachof electrodes 30 b, 30 c and 30 d are spaced proximally from therespective adjacent electrode 30 a, 30 b and 30 c by a respectiveinterelectrode distance 34, 35 and 36.

Each electrode 30 a-30 d is shown have equivalent electrode lengths 31.In other examples, however, electrodes 30 a-30 d may have electrodelengths 31 that are different from each other in order to optimizeplacement of the electrodes 30 or the resulting electrical field ofstimulation relative to targeted stimulation sites corresponding to leftand right portions of the HGN or branches thereof and/or motor points ofthe GG and GH muscles. The interelectrode spacings between electrodes 30a, 30 b, 30 c, and 30 d are shown to be approximately equal in FIG. 3,however they may also be different from each other in order to optimizeplacement of electrodes 30 relative to the targeted stimulation sites orthe resulting electrical field of stimulation relative to targetedstimulation sites corresponding to left and right hypoglossal nerves orbranches of hypoglossal nerves and/or motor points of protrusor muscles42 a, 42, or 46.

In some examples, electrodes 30 a and 30 b form an anode and cathodepair for delivering bipolar stimulation in one portion of the protrusormuscles, e.g., either the left or right GG and/or GH muscles or either aproximal or distal portion of the GG and/or GH muscles. Electrodes 30 cand 30 d may form a second anode and cathode pair for delivering bipolarstimulation in a different portion of the protrusor muscles (e.g., theother of the left or right portions or the other of the proximal ordistal portions). Accordingly, the interelectrode spacing 35 between thetwo bipolar pairs 30 a-30 b and 30 c-30 d may be different than theinterelectrode spacing 34 and 36 between the anode and cathode withineach bipolar pair 30 a-30 b and 30 c-30 d.

In one example, the total distance encompassed by electrodes 30 a-30 dalong the lead body 22 may be about 20 millimeter, 25 millimeters, or 30millimeters as examples. In one example, the total distance is between20 and 22 millimeters. The interelectrode spacings between a proximalelectrode pair 30 c-30 d and a distal electrode pair 30 a-30 b,respectively, may be between 2 and 6 mm, including all integer valuestherebetween. The interelectrode spacing separating the distal andproximal pairs 30 a-30 b and 30 c-30 d may be the same or different fromeach other and the spacing between individual electrodes of any suchpair.

In the example shown, each of electrodes 30 a-30 d is shown as acircumferential ring electrode which may be uniform in diameter withlead body 22. In other examples, electrodes 30 may include other typesof electrodes such as a tip electrode, a helical electrode, a coilelectrode, a segmented electrode, a button electrode as examples. Forinstance, the distal most electrode 30 a may be provided as a tipelectrode at the lead distal end 26 with the remaining three electrodes30 b, 30 c and 30 d being ring electrodes. When electrode 30 a ispositioned at the distal end 26, electrode 30 a may be a helicalelectrode configured to screw into the muscle tissue at the implant siteto additionally serve as a fixation member for anchoring the lead 20 atthe targeted therapy delivery site. In other examples, one or more ofelectrodes 30 a-d may be a hook electrode or barbed electrode to provideactive fixation of the lead 20 at the therapy delivery site.

Lead 20 may include one or more fixation member 32 for minimizing thelikelihood of lead migration. In the example shown, fixation member 32includes multiple sets of tines which engage the surrounding tissue whenlead 20 is positioned at the target therapy delivery site. The tines offixation member 32 may extend radially and proximally at an anglerelative to the longitudinal axis of lead body 22 to prevent or reduceretraction of lead body 22 in the proximal direction. Tines of fixationmember 32 may be collapsible against lead body 22 when lead 20 is heldwithin the confines of a lead delivery tool, e.g., a needle orintroducer, used to deploy lead 20 at the target implant site. Uponremoval of the lead delivery tool, the tines of fixation member 32 mayspread to a normally extended position to engage with surrounding tissueand resist proximal and lateral migration of lead body 22. In otherexamples, fixation member 32 may include one or more hooks, barbs,helices, or other fixation mechanisms extending from one or morelongitudinal locations along lead body 22 and/or lead distal end 26.Fixation member 32 may partially or wholly engage the GG, GH musclesand/or other muscles below the tongue, and/or other soft tissues of theneck, e.g., fat and connective tissue, when proximal end of lead body 20is tunneled to an implant pocket of pulse generator 12. In otherexamples, fixation member 32 may include one or more fixation mechanismslocated at other locations than the location shown in FIG. 3, includingat or proximate to distal end 26, between electrodes 30, or otherwisemore distally or more proximally than the location shown. The implantpocket of pulse generator 12 may be along the patient's neck 8 (seeFIG. 1) in the chest, or in another location as deemed appropriate bythe surgeon performing the implantation. Accordingly the length of theelongated lead body 22 from distal end 26 to the lead proximal end 24(FIG. 1) may be selected to extend from the target therapy delivery sitein the protrusor muscles to a location along the patient's neck wherethe pulse generator 12 is implanted. This length may be up to 10 cm orup to 20 cm as examples but may generally be 25 cm or less, thoughlonger or shorter lead body lengths may be used depending on the anatomyand size of the individual patient.

FIG. 2 is a conceptual diagram 120 of the lead 20 deployed fordelivering OSA therapy according to another example. In this example,lead 20 carrying electrodes 30 is advanced approximately along orparallel to midline 102 of tongue 40. In the example shown, lead body 22is shown approximately centered along midline 102, however in otherexamples lead body 22 may be laterally offset from midline 102 in theleft or right directions but is generally medial to both of the left HGN104L and the right HGN 104R. The distal end 26 of lead 20 may beinserted inferiorly to the body of tongue 40, e.g., at a percutaneousinsertion point along the submandibular triangle, in the musculaturebelow the floor of the oral cavity. The distal end 26 is advanced toposition electrodes 30 medially to the left and right HGNs 104L and104R, e.g., approximately midway between the hyoid bone the mentalprotuberance (chin). An electrical field produced by stimulation pulsesdelivered between any bipolar pair of electrodes selected fromelectrodes 30 may encompass a portion of both the left target region106L and the right target region 106R to produce bilateral stimulationof the HGNs 104L and 104R and therefore bilateral recruitment of theprotrusor muscles. Bilateral recruitment of the protrusor muscles mayprovide greater airway opening than unilateral stimulation that isgenerally performed using a nerve cuff electrode along the HGN. Forexample, electrical stimulation pulses delivered using electrodes 30 aand 30 b may produce electrical field 122 (shown conceptually)encompassing a portion of both of the left and right target regions 106Land 106R. Electrical stimulation pulses delivered using electrodes 30 cand 30 d may produce electrical field 124 (shown conceptually)encompassing a portion of both of the left and right target regions 106Land 106R. The portions of the left and right target regions 106L and106R encompassed by electrical field 122 are posterior portions relativethe portions of the left and right target regions 106L and 106Rencompassed by electrical field 124.

In some examples, electrical stimulation is delivered by pulse generator12 by sequentially selecting different electrode pairs from among theavailable electrodes 30 to sequentially recruit different bilateralanterior and bilateral posterior portions of the HGNs 104L and 104R.This electrode selection may result in recruitment of different anteriorand posterior portions of the protrusor muscles. The sequentialselection of different electrode pairs may be overlapping ornon-overlapping. The electrical stimulation is delivered throughout anextended time period encompassing multiple respiratory cyclesindependent of the timing of respiratory cycles to maintain a protrudedstate of tongue 40 from the beginning of the time period to the end ofthe time period. The electrodes 30 may be selected in bipolar pairscomprising the most distal pair 30 a and 30 b, the outermost pair 30 aand 30 d, the innermost pair 30 b and 30 c, the most proximal pair 30 cand 30 d or alternating electrodes along lead body 22, e.g., 30 a and 30c or 30 b and 30 d. Sequential selection of two or more differentelectrode pairs allows for sequential recruitment of different portionsof the protrusor muscles to reduce the likelihood of fatigue.

In some examples, electrical stimulation delivered using an electrodepair, e.g., 30 a and 30 b, that is relatively more distal along distallead portion 28 and implanted relatively anteriorly along tongue 40 mayrecruit a greater portion of anterior muscle fibers, e.g., within the GGmuscle. Electrical stimulation delivered using an electrode pair, e.g.,30 c and 30 d, that is relatively more proximal along distal leadportion 28 and implanted relatively posteriorly along tongue 40 mayrecruit a greater portion of posterior muscle fibers, e.g., within theGH muscle. Sequential selection of electrodes 30 for deliveringelectrical stimulation pulses allows sequential recruitment inoverlapping or non-overlapping patterns of anterior and posteriorportions of the protrusor muscles to sustain the tongue in a protrudedstate throughout the extended time period while reducing or avoidingmuscle fatigue.

FIG. 4 is a conceptual diagram of the distal portion of a dual leadsystem for delivering OSA therapy. In this example, one lead 20 isadvanced anteriorly approximately parallel to midline 102 and offset,e.g. by 5-8 millimeters to the left of midline 102, to position distalportion 28 and electrodes 30 in or adjacent to the left target region106L. A second lead 220 is advanced anteriorly approximately parallel tomidline 102 but offset laterally to the right of midline 102 to positiondistal portion 228 and electrodes 230 in or adjacent the right targetregion 106R. Lead 20 may be inserted from a left lateral or posteriorapproach of the body of tongue 40, and lead 230 may be inserted from aright lateral or posterior approach of the body of tongue 40. In otherexamples, both leads 20 and 220 may be inserted from only a left or onlya right approach with one lead traversing midline 102 to position theelectrodes 30 or 230 along the opposite side of midline 102 from theapproaching side. Lead 20 and/or lead 220 may be advanced at an obliqueangle relative to midline 102 but may not cross midline 102. In otherexamples, one or both leads 20 and 220 may approach and cross midline102 at an oblique angle such that one or both of distal portions 28 and228 extend in or adjacent to both the right and left target regions 106Land 106R, similar to the orientation shown in FIG. 6.

In the example shown, relatively more localized control of therecruitment of left, right, anterior and posterior portions of theprotrusor muscles may be achieve by selecting different electrode pairsfrom among the electrodes 30 a through 30 d and 230 a through 230 d. Forexample, any combination of electrodes 30 a through 30 d may be selectedfor delivering electrical stimulation pulses to the left portions of theprotrusor muscles. More distal electrodes 30 a and 30 b may be selectedfor stimulation of more anterior portions of the left protrusor muscles(corresponding to electrical field 144) and more proximal electrodes 30c and 30 d may be selected for stimulation of more posterior portions ofthe left protrusor muscles (corresponding to electrical field 142). Anycombination of electrodes 230 a through 230 d may be selected fordelivering electrical stimulation pulses to the right portions of theprotrusor muscles. More distal electrodes 230 a and 230 b may beselected for stimulation of more anterior portions of the rightprotrusor muscles (corresponding to electrical field 154) and moreproximal electrodes 230 c and 230 d may be selected for stimulation ofmore posterior portions of the right protrusor muscles (corresponding toelectrical field 152).

Switching circuit 96 may be configured to select electrode pairs thatinclude one electrode on one of leads 20 or 220 and another electrode onthe other lead 20 or 220 to produce an electrical field (not shown) thatencompasses portions of both the left target region 106L and the righttarget region 106R simultaneously for bilateral stimulation. Anycombination of the available electrodes 30 a through 30 d and electrodes230 a through 230 d may be selected as two or more bipolar pairs, whichare selected in a repeated, sequential pattern to sequentially recruitdifferent portions of the two target regions 106L and 106R. Thesequential selection of electrode pairs may be overlapping ornon-overlapping, but electrical stimulation pulses are delivered withoutinterruption at one or more selected frequencies throughout an extendedtime period to maintain tongue 40 in a protruded state from thebeginning of the time period to the end of the time period, encompassingmultiple respiratory cycles.

In the example of FIG. 4 including two leads, two pairs of electrodesmay be selected simultaneously and sequentially with one or more otherpairs of electrodes. For example, electrodes 30 a and 30 b may beselected as one bipolar pair and electrodes 230 c and 230 d may beselected as a second bipolar pair for simultaneous stimulation of theleft, anterior portion of the target region 106L and the right posteriorportion of the target region 106R. The electrodes 30 c and 30 d may beselected as the next bipolar pair from lead 20, simultaneously withelectrodes 230 a and 230 b selected as the next bipolar pair from lead220. In this way, electrical stimulation may be delivered bilaterally,alternating between posterior and anterior regions on each side. Theanterior left (30 a and 30 b) and posterior right (230 c and 230 d)bipolar pairs may be selected first, and the posterior left (30 c and 30d) and anterior right (230 a and 230 b) bipolar pairs may be selectedsecond in a repeated, alternating fashion to maintain tongue 40 in aprotruded state continuously during an extended time period encompassingmultiple respiratory cycles. In other examples, both of the anteriorpairs (30 a-30 b and 230 a-230 b) may be selected simultaneously first,and both the posterior pairs (30 c-30 d and 230 c-230 d) may be selectedsimultaneously second, sequentially following the anterior pairs. Inthis way, continuous bilateral stimulation may be achieved whilesequentially alternating between posterior and anterior portions toavoid or reduce fatigue. In contrast to other OSA therapy systems thatrely on a sensor for sensing the inspiratory phase of respiration tocoordinate the therapy with the inspiratory phase, the intramuscularelectrodes 30 positioned to stimulate different portions of theprotrusor muscles do not require synchronization to the respiratorycycle. Alternation of stimulation locations within the protrusor musclesallows different portions of the muscles to rest while other portionsare activated to avoid collapse of the tongue against the upper airwaywhile also avoiding muscle fatigue.

It is to be understood that more or fewer than the four electrodes shownin the examples presented herein may be included along the distalportion of a lead used in conjunction with the OSA therapy techniquesdisclosed herein. A lead carrying multiple electrodes for delivering OSAtherapy may include 2, 3, 5, 6 or other selected number of electrodes.When the lead includes only two electrodes, a second lead having atleast one electrode may be included to provide at least two differentbipolar electrode pairs for sequential stimulation of different portionsof the right and/or left medial HGNs. Furthermore, while the selectedelectrode pairs are generally referred to herein as “bipolar pair”including one cathode and one return anode, it is recognized that threeor more electrodes may be selected at a time to provide desiredelectrical field or stimulation vector for recruiting a desired portionof the protrusor muscles. Accordingly, the cathode of a bipolar “pair”may include one or more electrodes selected simultaneously from theavailable electrodes and/or the anode of the bipolar “pair” may includeone or more electrodes selected simultaneously from the availableelectrodes.

FIG. 5 timing diagram illustrating a method performed by pulse generator12 for delivering selective stimulation to the protrusor muscles forpromoting upper airway patency during sleep according to one example.Electrical stimulation is delivered over a therapy time period 401having a starting time 403 and an ending time (not shown). Electricalstimulation pulses that are delivered when pulse generator sequentiallyselects a first bipolar electrode pair 402 and a second bipolarelectrode pair 412 in an alternating, repeating manner are shown. Thefirst and second bipolar electrode pairs 402 and 412 may correspond toany two different electrode pairs described in the examples above inconjunction with FIGS. 3-4.

A first train of electrical pulses 406 is shown starting at the onset403 or therapy time period 401. The first train of electrical pulses 406is delivered using bipolar electrode pair 402 for a duty cycle timeinterval 404. The first train of electrical pulses 406 has a pulseamplitude 405 and pulse frequency, e.g., 20 to 50 Hz, defined by theinterpulse intervals 407. The first train of electrical pulses 406, alsoreferred to as “pulse train” 406, may have a ramp on portion 408 duringwhich the pulse amplitude is gradually increased from a starting voltageamplitude up to pulse voltage amplitude 405. In other examples, thepulse width may be gradually increased. In this way the delivered pulseenergy is gradually increased to promote a gentle transition from therelaxed, non-stimulated state to the protruded state of the tongue.

The train of electrical pulses 406 may include a ramp off portion 410during which the pulse amplitude (and/or pulse width) is decrementedfrom the pulse voltage amplitude 405 to an ending amplitude at theexpiration of the duty cycle time interval 404. In other examples, pulsetrain 406 may include a ramp on portion 408 and no ramp off portion 410.In this case, the last pulse of pulse train 406 delivered at theexpiration of duty cycle time interval 404 may be delivered at the fullpulse voltage amplitude 405. Upon expiration of the duty cycle timeinterval 404, electrical stimulation delivery via bipolar electrode pair402 is terminated.

In the example shown, a second electrode pair 412 is selected when dutycycle time interval 404 is expiring. The second electrode pair 412 maybe selected such that delivery of electrical stimulation pulse train 416starts a ramp on portion 418 that is simultaneous with the ramp offportion 410 of train 406. In other examples, the ramp on portion 418 ofpulse train 416 may start at the expiration of the first duty cycle timeinterval 404. When pulse train 406 does not include a ramp off portion410, the pulse train 416 may be started such that the ramp on portion418 ends just before, just after or coincidentally with the expirationof duty cycle time interval 404. The second pulse train 416 has aduration of duty cycle time interval 414 and may end with an optionalramp off portion 420, which may overlap with the ramp on portion of thenext pulse train delivered using the first electrode pair 402.

In this example, pulse trains 406 and 416 are shown to be equivalent inamplitude 405 and 415, pulse width, pulse frequency (and inter pulseinterval 407), and duty cycle time interval 404 and 414. It iscontemplated, however, that each of the stimulation control parametersused to control delivery of the sequential pulse trains 406 and 416 maybe separately controlled and set to different values as needed toachieve a desired sustained protrusion of tongue 40 while avoiding orminimizing fatigue.

The sequential pulse trains 406 and 416 are delivered using twodifferent electrode pairs 402 and 412 such that different portions ofthe protrusor muscles are recruited by the pulse trains 406 and 416allowing one portion to rest while the other is being stimulated.However, pulse trains 404 and 406 occur in a sequential overlapping ornon-overlapping manner such that electrical pulses are delivered at oneor more selected frequencies for the entire duration of the therapy timeperiod 401 to sustain the tongue in a protruded state throughout timeperiod 401. It is to be understood that the relative down and/or forwardposition of the protruded tongue may shift or change as differentelectrode pairs are selected but the tongue remains in a protruded statethroughout therapy time period 401.

At times, the pulse trains 404 and 406 may be overlapping tosimultaneously recruit the left and right GG and/or GH muscles to createa relatively greater force (compared to recruitment of a single side) topull the tongue forward to open an obstructed upper airway. In somecases, the overlapping pulse trains 404 and 406 may cause temporaryfatigue of the protrusor muscles along the left or right side but thetemporary fatigue may improve the therapy effectiveness to ensure anopen upper airway during an apneic episode. Recovery from fatigue willoccur between duty cycles and at the end of an apneic episode. Dutycycle lengths may vary between patients depending on the fatigueproperties of the individual patient. Control circuit 80 may control theduty cycle on time in a manner that minimizes or avoids fatigue in aclosed loop system using a signal from sensor 86, e.g., a motion sensorsignal and or electromyography (EMG) signal correlated protrusor musclecontraction force and subsequent fatigue.

FIG. 6 is a timing diagram 500 of a method for delivering OSA therapy bypulse generator 12 according to another example. In this example, atherapy delivery time period 501 is started at 503 with a ramp oninterval 506 delivered using a first bipolar electrode pair 502. Theramp on interval 506 is followed by a duty cycle time interval 504. Uponexpiration of the duty cycle time interval 504, a second bipolarelectrode pair 512 is selected for delivering electrical stimulationpulses for a second duty cycle time interval 514. A third duty cycletime interval 524 starts upon the expiration of the second duty cycletime interval 514, and stimulation pulses are delivered by selecting athird bipolar electrode pair 522 different than the first two pairs 502and 512. A fourth bipolar pair 532 is selected upon expiration of thethird duty cycle time interval 524 and used to deliver stimulationpulses over the fourth duty cycle time interval 534. Upon expiration ofthe fourth duty cycle time interval 534, the sequence is repeatedbeginning with duty cycle time interval 504 again.

In this example, four different bipolar pairs are selected in sequence.The four different bipolar electrode pairs may differ by at least oneelectrode and/or the polarity of another bipolar electrode pair. Forexample, when a single quadripolar lead 20 is used, the four bipolarpairs may include 30 a-30 b, 30 b-30 c, 30 c-30 d and 30 a-30 d. Theportions of the protrusor muscles recruited by the four different pairsmay not be mutually exclusive since the electrical fields of the fourdifferent pairs may stimulate some of the same nerve fibers. Fourdifferent portions of the protrusor muscles may be recruited, which mayinclude overlapping portions. The relatively long recovery periods 540,542, 544 and 546 between respective duty cycle time intervals allowseach different portion of the protrusor muscles to recover before thenext duty cycle. When recruited muscle portions overlap between selectedelectrode pairs, the bipolar electrode pairs may be selected in asequence that avoids stimulating the overlapping recruited muscleportions consecutively. All recruited muscle portions are allowed torecover during at least a portion of each respective recovery period540, 54, 544 and/or 546. For example, if the bipolar electrode pair 502and the bipolar electrode pair 522 recruit overlapping portions of theprotrusor muscles, the recruited portions may still recover during thesecond duty cycle time interval 514 and during the fourth duty cycletime interval 534.

The duration of each duty cycle time interval, 504, 514, 524 and 534,may be the same or different from each other, resulting in the same ordifferent overall duty cycles. For example, when four bipolar electrodepairs are sequentially selected, stimulation delivery for eachindividual pair may be a 25% duty cycle. In other examples, acombination of different duty cycles, e.g., 30%, 10%, 40% and 20%, couldbe selected in order to promote sustained protrusion of the tongue withadequate airway opening while minimizing or avoiding fatigue. Theselection of duty cycle may depend on the particular muscles or muscleportions being recruited and the associated response (position) of thetongue to the stimulation for a given electrode pair selection.

The stimulation control parameters used during each of the duty cycletime intervals 504, 514, 524, and 534 for delivering electrical pulsesusing each of the different bipolar electrode pairs 502, 512, 522 and532 may be the same or different. As shown, a different pulse voltageamplitude and a different interpulse interval and resulting pulse trainfrequency may be used. The pulse amplitude, pulse width, pulsefrequency, pulse shape or other pulse control parameters may becontrolled according to settings selected for each bipolar electrodepair.

In the example shown, one ramp on portion 506 of the stimulationprotocol is shown at the onset of the therapy delivery time period 501.Once the stimulation is ramped up to position the tongue in a protrudedposition, no other subsequent duty cycle time intervals 504 (other thanthe first one), 514, 524 and 534 may include or be proceeded by a rampon portion. In other examples, a ramp on portion may precede each dutycycle time interval (or be included in the duty cycle time interval asshown in FIG. 5) and may overlap with the preceding duty cycle timeinterval. No ramp off portions are shown in the example of FIG. 6. Inother examples, ramp off portions may follow or be included in each dutycycle time interval 504, 514, 524 and 534 and may overlap with the onsetof the next duty cycle time interval as shown in FIG. 5. In someexamples, only the last duty cycle time interval (not shown in FIG. 6)may include or be immediately followed by a ramp off portion to gentlyallow the tongue to return to a relaxed position at the end of thetherapy delivery time period 501.

Following implantation as depicted in FIGS. 3 and 4 and calibration bythe surgeon or other caregiver, the INS 10 is ready for use. Inaccordance with one aspect of the disclosure, the INS system 10 ismanually switched on by the patient as part of their routine prior tosleeping. This may be a function of the external programmer 50, oranother similar device that can communicate with the pulse generator 12via the telemetry circuit 88. A delay period may be programmed into thesoftware or firmware employed by the control circuit 80. The delayperiod allows the patient a period to fall asleep before therapy isbegun. The period may be established for the patient based on a varietyof factors, including an average time to sleep observed during, forexample, a sleep study and may be adjusted by the patient via theexternal programmer 50. Without the delay period, the patient wouldimmediately begin to experience the effects of stimulating the protrusormuscles, which though not dangerous or painful, can be observed and maybe considered annoying to experience while awake.

As will be appreciated, manual switching as described above, is notalways a desirable feature in an implantable device associated withsleeping. In a further aspect of the disclosure, OSA therapy may bestarted and stopped at scheduled times of day. Control circuit 80 mayinclude a clock for scheduling the time that OSA therapy is started andstopped by therapy delivery circuit 84. Many patients, however, are notas rigorous regarding their schedules as would be desired to make thescheduling most effective. Further, the patient may find themselves at asocial gathering or other affair at a time where they are normallyscheduled for sleeping. Additionally, or alternatively, the patient mayfind themselves taking an unscheduled nap in a motor vehicle, plane, ortrain, and not have an opportunity to initiate or schedule therapy.Since OSA is often co-morbid with heart related diseases any instancesof experiencing OSA can have complicating factors affecting thepatient's heart. Thus, sensing of sleeping conditions and initiation oftherapy are desirable. One aspect of the disclosure is directed to amechanism of initiating therapy based on a detected state of the tone ofthe protrusor muscles.

In accordance with the disclosure, and as noted above, the electrodes 30either alone or in combination with the sensor 86 can be configured todetect electromyography (EMG) signals. Electromyography is a techniqueof evaluating and recording the electrical activity produced by skeletalmuscles. An electromyograph detects the electrical potential generatedby muscle cells when the cells are electrically or neurologicallyactivated. FIG. 7A, in an upper plot depicts an EMG signal observed in agenioglossus muscle (GG) 42, in a patient during normal breathing. Thelower plot in FIG. 7A depicts the pharyngeal pressure during the sameperiod as the EMG signal in the upper plot. As can be seen in FIG. 7A,during breathing as the pharyngeal pressure drops, consistent withinhalation, the EMG signal significantly increases. Those of skill inthe art will recognize that this increase in EMG signal duringbreathing, signifying stimulation of the muscles of the tongue such asthe genioglossus muscle (GG) 42, ensures that the airway is not closedor collapsed easing the ability of the subject to take a breath. Thatis, at periods of high EMG signal the protrusor muscles have acontracted tonal state. At periods where there is a low EMG signal, theprotrusor muscles have a relaxed tonal state.

FIG. 7B depicts a comparison of observed EMG signals observed in theprotrusor muscles of two sets of subjects. For all subjects, the EMGsignal declines when the subject is in a sleeping state as compared to awakeful state. However, significantly for the instant disclosure,subjects who are experiencing an OSA episode have a dramatically lowerEMG signal. This reduced EMG signal is evidence of a reduced tonal stateof the protrusor muscles of the subjects experiencing OSA. FIG. 8depicts similar data for comparison of the EMG signals during REM,non-REM, quiet wakefulness, and active wakefulness of subjects. Thisdata confirms the top line of FIG. 7B that when asleep, the EMG signalsare reduced, and as noted in FIG. 7B, that reduction is more pronouncedand in subjects experiencing an OSA event.

In accordance with one aspect of the disclosure, when a stimulationpulse is not being delivered by electrodes 30 a-30 d, the electrodes canbe employed to detect the electrical potential of muscles. That is, theelectrodes 30 a-30 d can detect the EMG signals that are being appliedto the protrusor muscles by the patient's neural system. These signalscan be communicated to the control circuit 80 for monitoring andapplication of rules in the software or firmware stored therein. Inother examples, dedicated EMG sensing electrodes may be carried byhousing 15 and/or lead body 22 and coupled to sensor 86 for EMG signalmonitoring. EMG signal monitoring by control circuit 80 allows fordetection of a low tonal state of the GG and/or GH muscles. Withreference to FIG. 7A a low tonal state (i.e., low incidence of EMGsignals) indicates both a likelihood of the patient being asleep and asusceptibility to upper airway collapse. Detection of low tonal state ofthe protrusor muscles may either alone or in combination with othersensor data, e.g., detection of the pose of the patient indicating thatthey are in a reclined position or the detection of a heart rateconsistent with sleeping, be used to initiate therapy and prevent theonset of an OSA event. Thus, the EMG signals may be used by controlcircuit 80 to detect a sleep state and/or low tonal state of theprotrusor muscles for use in controlling therapy delivery circuit 84 fordelivering stimulation pulses to cause protrusion of the patient'stongue. As will be appreciated, in the detection of the EMG signals avariety of bandpass filtering, rectification, and normalization may beemployed by the control circuit 80, or intervening hardware to produce auseable signal providing a clear indication of the state of theprotrusor muscles. An example of such processing of the EMG signal isdepicted in FIG. 9.

EMG monitoring may further be used in monitoring for fatigue of thestimulated GG and/or GH muscles. If fatigue of the muscles is detected,control circuit 80 may alter to control the duty cycle of electricalstimulation pulse trains delivered by therapy delivery circuit 84 tominimize or avoid fatigue and/or allow adequate fatigue recovery timebetween duty cycle on times. In this manner, Sensor 86 may be configuredto produce a signal that is correlated to protrusor muscle tonal statefor use by control circuit 80 for detecting a low tonal state predictiveof upper airway obstruction, detecting protrusor muscle fatigue, and/ordetecting a protruded state of tongue 40. Therapy delivery circuit 84may be configured to respond to a detection of the protrusor muscletonal state by control circuit 80 by adjusting one or more controlparameters used to control stimulation pulse delivery.

As noted above, the EMG monitoring may not be the only signal employedby the pulse generator 12, and particularly the control circuit 80 indetermining the level of wakefulness. As an example, sensor 86 mayinclude an accelerometer that can provide an indication of motion of thepatient. Further, where the accelerometer 86 is a three-axisaccelerometer, a posture of the patient may be determined. Additionally,an accelerometer may be employed to detect snoring sounds and physicalmovements of the patient. Still further, a temperature sensor may beemployed in which the diurnal temperature of a patient is measured andstored in memory as are sleeping temperatures. The sensor 86 may also beone or more accelerometers employed to detect the heartrate of apatient. In another example, sensor 86 may be an accelerometer employedto detect the rate of breathing or the volume of airflow, into or out ofthe patient. Volume of airflow may be determined by placing theaccelerometer at a point on a patient's chest and comparing the travelof the accelerometer to previously observed lung volume data that hasbeen correlated to the sensor 86 movement data. Breathing rate can bedetermined by simply monitoring the change in direction of theaccelerometer.

Still further, the sensor 86 may be an implantable pulse-oximeteruseable to measure the blood oxygen saturation levels. In one examplethe pulse-oximeter is a cuff placed substantially around a blood vesseland measuring the blood-oxygenation levels using a light source as isknown in the art. As described herein, the sensor 86 may be one orseveral of the various types of sensors described herein.

The sensor 86 may be an ECG sensor. ECG is a recording of the electricalactivity of the heart over a period of time. While an ECG typicallyemploys sensors placed on the skin, an effective ECG can be employed inan implantable device wherein at least two electrodes separated by adistance (e.g., at least about 35 mm) are employed to detect electricalchanges caused by the cardiac depolarization and repolarization duringeach cardiac cycle.

A further aspect of the disclosure is described in connection with FIGS.10 and 11 in which a simplified diagram of an INS system is depicted,and a method of the systems operation are described. The system 600includes an INS device 10, an external programmer 50, a server 602 incommunication with the external programmer and a remote computer 604 incommunication with the server 602. Prior to implantation of an INS 10,patients typically undergo a patient assessment (step 702) one or moreanalyses in conjunction with their doctor. During this analysis avariety of self-reported issues may be identified including daytimesleepiness, interrupted snoring, gasping, co-morbidities, etc. The datarelated to these issues may be stored on the server 602 as part of thepatient electronic medical records (EMR) or as part of a specific OSAtreatment and remediation file. The discussions with the medicalprovider may lead to an initial diagnosis of OSA. This initial diagnosisis typically confirmed through the use of one or more sleep studies ofthe patient. During the sleep study a wide variety of physiological datais gathered as well as some self-reported data. For example, the heartrate, blood oxygen saturation levels, temperature, anelectroencephalogram (EEG), electrocardiogram (ECG), total sleep,quality of sleep, sleep efficiency, sleep stages, number of arousals(less than 15 s), number of awakenings (greater than 15 s), ApneaHypopnea Index as well as others. These data may be recorded by remotecomputer 604, either directly or via additional hardware, and saved onthe remote server 602 (step 704).

These collected data from the sleep study, along with the data collectedby the medical provider may be used to generate an initial set ofstimulation parameters (e.g., pulse width, frequency, amplitude, pairingof electrodes, etc.) for the INS 10 (step 706). This may be in partbased on larger population studies to identify some aspects of moreglobal therapy parameters. The initial stimulation parameters may be seteither at remote computer 604 or directly at external programmer 50, andin either event may be saved a server 602 (e.g., a cloud computerstorage device), for access by either device. And the externalprogrammer 50 can be employed to install the initial stimulationparameters in the INS 10 (step 708). Often, the patient is permitted toutilize the INS 10 for a period of time, and a subsequent sleep studymay be performed. From this second sleep study, the initial stimulationparameters may be altered, or additional surgery may be recommended tothose who do not respond to stimulation therapy. Further sleep studiesmay be required periodically to adjust the stimulation parametersettings in an effort to improve the therapy of the individual patient.

In accordance with the present disclosure, the data collected from thesensor 86 may be combined with various self-reported data that a usermay input via a user interface on the external programmer 50 andutilized to replace at least the second sleep study, and possibly thefirst as well. The external programmer 50, or another device incommunication with the server 602, presents the patient with a userinterface. The user interface may be presented to the user on a periodicbasis including daily, weekly, bi-weekly, or monthly. In accordance,with the daily embodiment, the user interface may request that thepatient input various self-reporting data. This can include nightlyalcohol intake, smoking, stress, the time the patient went to bed, thepatient's perception of the quality of the last night's sleep,tiredness, discomfort, pain or soreness of the protrusor musclespotentially caused by the stimulation, etc. Additionally, data fromother appliances may also be reported. For example, may patientssuffering from OSA also suffer from high blood pressure, and may be on aregimen of periodically testing their blood pressure. This bloodpressure data may be self-reported via the user interface. Similarly, ifthe patient is a diabetic, they may need to test their blood sugarlevels both before and after sleep. These data too may be self-reportedvia the user interface. In addition, the patient may be asked to answerthe inquiries of the Eppsworth Sleepiness Scale (ESS). In oneembodiment, the ESS inquiry may be requested of the patient at adifferent interval that the other data. In this way the ESS can be usedas one gauge of the effectiveness of the therapy.

As noted above, the sensor 86 can provide a variety of data dependentupon how it is configured. As one example using the EMG data, a sleepstart and end time may be determined. Using one or more accelerometersand a variety of bandpass filtering position, activity (arousals vsawakenings), sleep stages, respiration rate, and heart rate can becollected. This data can be reported to the control circuit 80 andstored in memory 82 at least temporarily. The external programmer 50 canbe set to automatically interface with the INS 10 every day, or atanother periodic interval. The external programmer 50 can then downloadthe sensor data via the telemetry circuit and communicate the sensordata from the INS and self-reported data entered via the user-interfaceto the server 602 (step 710).

The server 602 may include thereon one or more software applications.One of these applications may review the data received from the externalprogrammer 50 and assign a value to each datapoint received. Thesevalues can be analyzed, and a sleep score determined based on thereceived sensor and self-reported data (step 712). The sleep scoreprovides an overall assessment of the patient's sleep that can beassessed by both the patient and the medical provider. As will beapparent some data points may be more important to assessing the overallsleep of the patient thus some form of scaling of the values may berequired. The application will also be able to flag any relevant datasignificant to a poor sleep score. For example, if the patient reportedseveral alcoholic drinks the evening before the data resulting in thepoor sleep score was recorded, this might be a highly relevant factor,and indicate that the sleep score for that day is not an accurateindicator of the effectiveness of the current stimulation parameters.

Regardless, the sleep score may then be recorded as part of thepatient's sleep record and the score reported to a medical provider viathe remote computer 604 (step 714) . This data may be viewed in avariety of ways to provide the medical provider an assessment of thecurrent stimulation parameters. For example, the medical provider mayview the daily results, an average over a period of time, a graphicalrepresentation of the sleep score or a percentage or rate of change (ifany) from the preceding reporting period. By periodically assessing theeffectiveness of the parameters and comparing the effectiveness to theadditional self-reported data a multi-pronged analysis can beundertaken. In one example if the patient's data indicates that thetherapy is effective in achieving quality sleep with few incidents ofOSA, but the patient expresses a feeling of soreness or fatigue of theprotrusor muscles, the stimulation parameters may be changed to increasethe frequency of the switching between bi-polar pairs and to prolong theinterval between any set of bi-polar pairs being stimulated.Alternatively, the amplitude of the signal may be reduced. Further,following further sampling of the data collected by the sensor 86 andself-reported by the patient via the user interface, if the first ofthese is not effective, the second may be attempted. In this way, themedical provider is able to proceed in a stepwise fashion of alteringthe stimulation parameters, make adjustments, and observing the resultsof those adjustments while considering not just the self-reported data.This collection of data and reporting of a sleep score (steps 710-714)may be iterative repeated prior to advancing to the next step. One ofskill in the art will recognize that the remote computer may in fact bean external programmer 50 configured for physician or medical careprovider's use.

In a further aspect of the disclosure, the server 602 may collect or bein communication one or more further servers receiving similar data fromother patients. The entirety of the collected data may then be analyzedby one or more neural networks to assess the combined data and toidentify patterns within the data to provide a global assessment ofstimulation parameters and effectiveness of the stimulation pattens whenapplied across a wide array of patients. Some of these patients willhave similar comorbidities, and others will not. By further assessmentof the data the neural network can seek out similar groups of patientsand provide refined initial stimulation parameters for the subgroupbased on these similarities (e.g., age, demographics, weight, heartdisease, blood pressure, etc.). The neural network may also be employedto assess an individual patient to provide individualized guidance onupdating stimulation parameters. In a similar fashion, the server mayinclude one or more applications employing fuzzy logic to analyze thedata from both an individual and from the broader community of patientsto provide suggestions for updating the stimulation parameters (step716). In both the use of neural networks and fuzzy logic the applicationon the server 602 may present the medical provider with the option toreject the suggested updated stimulation parameters (step 718) or toaccept or modify the suggested updated stimulation parameters (step720). As will be appreciated, the medical provider may forgo the use ofeither the neural network or fuzzy logic and update or modify thestimulation parameters. Once the updated stimulation parameters areaccepted/modified by the medical provider the updated stimulationparameters are communicated to the external programmer 50 (step 722).Once received at the external programmer 50, the patient again may havethe option to accept the updated stimulation parameters (step 724) orreject the updated stimulation parameters (step 726). If accepted by thepatient the external programmer 50 can update the stimulation parameterson the INS (step 728). If at step 718 or 726 the updated stimulationparameters are rejected, the method simply returns to step 710.Similarly, after updating the stimulation parameters on the INS 10, theprocess similarly returns to step 710.

These updated stimulation parameters may be stored on the server 602until the next communication with the remote programmer 50, at whichtime the improved stimulation parameters may be downloaded to theexternal programmer 50. During the next collection of data from the INS10, the external programmer 50 may then download the updated stimulationparameters to the INS 10. In this way, the stimulation parameters of theINS updated, and the patient's sleep score improved. As would beexpected the user interface on the external programmer 50 would indicateto the patient that the new stimulation parameters are ready forinstalling on the INS, and it is at this point that steps 726 and 724may be performed.

A further aspect of the present disclosure is the presence of anartificial intelligence (AI) within the external programmer 50. The AImay have a limited mandate for purposes of safety of the patient tolimit the number of successive nights resulting in a poor sleep score.In one aspect of the disclosure, following the update of the stimulationparameters and receiving the data from the following night's sleep, theAI could analyze the data from sensor 86 and the self-reported data andmake an immediate assessment regarding the sleep score (step 730). Ifthe sleep score is bad the user interface may present the patient withthe ability to revert to the prior stimulation parameters until they caninterface with their medical provider regarding the prior bad night'ssleep (step 732). Of course, the AI may require more than a singlenight's data to identify the issue or have sufficient data to raiseconcerns with the patient. Further, the AI may be enabled to communicatea request for intervention directly to the medical provider via theserver 602 and remote computer 604.

In this way real actionable feedback on the effectiveness of stimulationparameters is provided to both the medical provider and to the patient.A continuum of care and assessment of the patient's experience with theINS device is enabled so that adverse results from therapy can berectified and behavioral modifications can be suggested to the patientbased on their self-reported data.

It will be appreciated by those of skill in the art that one or more ofthe calculations, assessments, and user interfaces described hereinabove with respect to the server 602 and the remote computer 604 mayalso be performed directly at the external programmer 50. In someembodiments this may provide for near instant feedback to the patientregarding a prior night's sleep via a user interface on the externalprogrammer. In other embodiments, where the external programmer 50 is ofa type typically used by the physician during an office visit, thecapabilities and functions of the external programmer 50 can be morerobust and potentially even eliminate or at least reduce the use of theserver 602 and remote computer 604. As a further, example, inapplications employing an AI, the AI may be trained to perform all ofthe assessments and analyses of the server and offer up the suggestionsfor modification of the stimulation parameters to the patient or careprovider. allowing a greater depth of understanding of the therapy,efficacy, and assessment of possible changes, without necessarilyrequiring access to the data stored on the server 602 or theapplications operating thereon. And in yet a further example, the AI onthe external programmer 50 may assess the data received from the INS 10and make adjustments to the stimulation parameters either autonomouslyor present them to the patient for acceptance. As will be appreciated,these updates may be bounded to prevent large changes in the stimulationparameters from occurring without intervention from a medical provider.

It should be understood that, depending on the example, certain acts orevents of any of the methods described herein can be performed in adifferent sequence, may be added, merged, or left out altogether (e.g.,not all described acts or events are necessary for the practice of themethod). Moreover, in certain examples, acts or events may be performedconcurrently, e.g., through multi-threaded processing, interruptprocessing, or multiple processors, rather than sequentially. Inaddition, while certain aspects of this disclosure are described asbeing performed by a single module or unit for purposes of clarity, itshould be understood that the techniques of this disclosure may beperformed by a combination of units or modules associated with, forexample, a medical device.

In one or more examples, the functions described may be implemented inhardware, software, firmware, or any combination thereof. If implementedin software, the functions may be stored as one or more instructions orcode on a computer-readable medium and executed by a hardware-basedprocessing unit. Computer-readable media may include computer-readablestorage media, which corresponds to a tangible medium such as datastorage media (e.g., RAM, ROM, EEPROM, flash memory, or any other mediumthat can be used to store desired program code in the form ofinstructions or data structures and that can be accessed by a computer).

Instructions may be executed by one or more processors, such as one ormore digital signal processors (DSPs), general purpose microprocessors,application specific integrated circuits (ASICs), field programmablelogic arrays (FPGAs), or other equivalent integrated or discrete logiccircuitry. Accordingly, the term “processor,” as used herein may referto any of the foregoing structure or any other structure suitable forimplementation of the techniques described herein. Also, the techniquescould be fully implemented in one or more circuits or logic elements.

Thus, an implantable medical device system has been presented in theforegoing description with reference to specific examples. It is to beunderstood that various aspects disclosed herein may be combined indifferent combinations than the specific combinations presented in theaccompanying drawings. It is appreciated that various modifications tothe referenced examples may be made without departing from the scope ofthe disclosure and the following claims.

We claim:
 1. An implantable neurostimulator (INS) comprising: anelectrical lead having formed thereon at least a pair of bi-polarelectrodes, wherein the electrical lead is configured for placement ofthe pair of bi-polar electrodes proximate protrusor muscles of a patientand configured to receive electromyography (EMG) signals; a pulsegenerator electrically connected to the electrical lead and configuredto deliver electrical energy to the pair of bi-polar electrodes, thepulse generator having therein a sensor and a control circuit, whereinthe sensor and control circuit are configured to receive the EMG signalsand determine a tonal state of the protrusor muscles in which the leadis placed.
 2. The implantable neurostimulator of claim 1, wherein thecontrol circuit is in electrical communication with a therapy deliverycircuit and causes the therapy delivery circuit to deliver electricalenergy to the bi-polar electrodes upon a determination that the EMGsignal is below a threshold value.
 3. The implantable neurostimulator ofclaim 1, wherein the control circuit is in electrical communication witha therapy delivery circuit and causes the therapy delivery circuit todeliver electrical energy to the bi-polar electrodes upon adetermination that the EMG signal is below a threshold value and a heartrate detected by the sensor is below a threshold.
 4. The implantableneurostimulator of claim 1, wherein the control circuit is in electricalcommunication with a therapy delivery circuit and causes the therapydelivery circuit to deliver electrical energy to the bi-polar electrodesupon a determination that the EMG signal is below a threshold value anda motion sensor determines that the INS is not moving.
 5. Theimplantable neurostimulator of claim 1, wherein the control circuit isin electrical communication with a therapy delivery circuit and causesthe therapy delivery circuit to deliver electrical energy to thebi-polar electrodes upon a determination that the EMG signal is below athreshold value and an acoustic sensor detects sounds consistent withsnoring.
 6. The implantable neurostimulator of claim 1, wherein thecontrol circuit is in electrical communication with a therapy deliverycircuit and causes the therapy delivery circuit to deliver electricalenergy to the bi-polar electrodes upon a determination that the EMGsignal is below a threshold value and a temperature sensor detects abody temperature consistent with sleeping.
 7. The implantableneurostimulator of claim 1, wherein the control circuit is in electricalcommunication with a therapy delivery circuit and causes the therapydelivery circuit to deliver electrical energy to the bi-polar electrodesupon a determination that the EMG signal is below a threshold value anda breathing rate sensor detects a breathing rate consistent withsleeping.
 8. A system comprising: an implantable neurostimulator (INS),including a lead having at least one pair of bi-polar electrodes, and apulse generator in electrical communication with the bi-polarelectrodes, the pulse generator including a sensor, a memory, a controlcircuit, and a telemetry circuit; an external programmer incommunication with the INS via the telemetry circuit; a server incommunication with the external programmer and including thereon anapplication configured to receive sensor data from the INS from theexternal programmer and assess a quality of the sleep of a patient inwhich the INS is implanted based on the received sensor data; and aremote computer in communication with the server and configured topresent an assessment of the quality of sleep of the patient.
 9. Thesystem of claim 8, further comprising a user interface presented on theexternal programmer and configured to receive a variety of self-reporteddata entered by the patient.
 10. The system of claim 9, wherein theapplication is further configured to assess the quality of the sleep ofa patient in which the INS is implanted based on the received sensordata and the self-reported data.
 11. The system of claim 10, wherein theassessment of the quality of sleep is presented in the form of a sleepscore.
 12. The system of claim 8, wherein the application is configuredto assess the quality of the sleep of a patient in which the INS isimplanted based on the received sensor data and self-reported dataentered via a user interface on the external programmer and to determinean set of suggested updated stimulation parameters for the INS.
 13. Thesystem of claim 12, wherein the received sensor data includes one ormore of a tonal state of protrusor muscles, heartrate, blood pressure,blood oxygen saturation, patient temperature, arousals, awakenings, andelectromyography data.
 14. The system of claim 12, wherein the updatedstimulation parameters are available of review, acceptance,modification, or rejection on the remote computer.
 15. The system ofclaim 14, wherein upon acceptance or modification of the updatedstimulation parameters, the updated stimulation parameters aretransmitted to the external programmer.
 16. The system of claim 15,wherein the external programmer transmits the updated stimulationparameters to the INS.
 17. A method of providing feedback for animplantable neurostimulator (INS), comprising: receiving sensor datafrom an INS having at least one lead implanted in a protrusor muscle ofa patient; receiving self-reporting data entered via a user interface;analyzing the sensor and self-reported data to determine a sleep score;recording the sleep score; and presenting the sleep score for analysis.18. The method according to claim 17, further comprising providingsuggestions for updating stimulation parameters of the INS.
 19. Themethod according to claim 18, further comprising updating the INS withthe updated stimulation parameters for application of stimulation to thepatient.
 20. The method according to claim 19, further comprisinganalyzing with an artificial intelligence the self-reported data andsensor data to determine whether a reversion to the stimulationparameters of the INS prior to the update is necessary.